Ferring Presents Phase 3 Data on SI-6603 for Lumbar Disc Herniation at NASS 2024

Ferring Pharmaceuticals and Seikagaku Corporation have presented the findings from two Phase 3 clinical trials assessing the effectiveness and safety of SI-6603 (condoliase) for treating radicular leg pain due to lumbar disc herniation (LDH). The data was shared at the North American Spine Society’s Annual Meeting, with results also published in The Spine Journal.

The studies were double-blind and controlled, involving patients who received either a single intradiscal injection of SI-6603 or a control (sham injection in the U.S., placebo in Japan) and were observed over 52 weeks. In the U.S. study, 341 participants were included (169 received SI-6603, 172 received the sham injection). In Japan, 163 participants took part (82 received SI-6603, 81 received the placebo).

Both studies met their primary endpoints, showing a significant reduction in worst leg pain at Week 13. The U.S. study showed a least squares mean (LSM) difference of -7.5 (p=0.0263), while the Japanese study had an LSM difference of -15.2 (p=0.001).

Dr. Kee Kim from the University of California, Davis, highlighted the limited current treatment options for radicular leg pain associated with LDH, emphasizing the potential of SI-6603 as a new therapeutic option. The most reported treatment-emergent adverse events (TEAEs) in the U.S. trial included spinal MRI abnormalities (28.1% for SI-6603, 9.2% for sham) and back pain (19.2% for SI-6603, 12.6% for sham). In Japan, the common TEAEs were back pain (36.6% for SI-6603, 33.3% for placebo) and leg pain (25.6% for SI-6603, 35.8% for placebo). There were no treatment-related serious adverse events (SAEs) in the U.S. study, and only one SAE (back pain) in the Japanese study potentially related to SI-6603.

The U.S. Phase 3 trial, known as the Discovery 6603 clinical trial (NCT03607838), involved participants aged 30 to 70 years with unilateral radiculopathy or radicular leg pain due to LDH. Participants were randomized 1:1 to receive either SI-6603 or a sham injection, followed by 52 weeks of observation. The primary endpoint was the change from baseline (CFB) to Week 13 in the worst leg pain over the past 24 hours, measured using the Visual Analogue Scale (VAS). Secondary endpoints included CFB in average worst leg pain at 52 weeks, percentage of participants with a negative straight leg raise test, and 50% responder rates for worst leg pain and the Oswestry Disability Index (ODI).

The Japanese Phase 3 trial also randomized participants 1:1 to receive a single injection of SI-6603 or a placebo, followed by 52 weeks of observation. The primary endpoint mirrored the U.S. study’s CFB to Week 13 in worst leg pain, assessed using the VAS. Secondary endpoints included CFB up to Week 52 in worst leg pain, herniation volume, and ODI score.

Lumbar disc herniation affects about 9 million adults in the U.S. annually. This condition occurs when the gel-like core of an intervertebral disc displaces through its outer membrane, pressing on the spinal nerve and causing pain. SI-6603 aims to alleviate this pain by reducing nerve root compression through a single intradiscal injection. Seikagaku developed SI-6603 and received marketing approval in Japan in March 2018, where it is sold as HERNICORE® through Kaken Pharmaceutical Co., Ltd.

Seikagaku and Ferring entered a licensing agreement in August 2016. Ferring plans to commercialize SI-6603 in the U.S. upon FDA approval and has rights to develop and market the product globally, excluding Japan.

Ferring Pharmaceuticals, headquartered in Saint-Prex, Switzerland, is known for its work in reproductive medicine, maternal health, gastroenterology, and orthopaedics, employing over 7,000 people and marketing its products in more than 100 countries.